Effects of microtrauma on joint structural changes in the Curdlan-injected SKG mouse model of ankylosing spondylitis.

Although microtrauma is considered a potential environmental factor in the development of ankylosing spondylitis (AS), there is a lack of experimental research regarding its precise contribution to disease pathogenesis. To induce physiological microtrauma, the right ankles of SKG mice were immobilized for a week using surgical plaster and a pipette tip to stimulate compensatory mechanical overload in the contralateral limb. Following the removal of the immobilization, the mice were intraperitoneally injected with 3 mg of Curdlan. In this model, the non-immobilized left ankle served as the microtraumatized group, while the immobilized right ankle served as the internal control. Arthritis severity was clinically scored weekly for 5 weeks. At 6 weeks, ankle, hip, and sacroiliac (SI) joint changes were evaluated using histological and micro-CT analyses. The microtraumatized (left) ankles of Curdlan-injected SKG mice exhibited exacerbated arthritis severity, synovitis, and enthesitis compared with the control ankles. Micro-CT analysis revealed a significantly elevated inflamed bone volume in the microtraumatized ankles. Immunohistochemistry showed markedly higher expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the synovium and enthesis of the microtraumatized ankles. Notably, distant pathological changes, including proteoglycan loss and joint space narrowing, were also observed in the left hip joints. Collectively, these findings indicate that compensatory microtrauma significantly exacerbates joint inflammation and pathological bone destruction in the Curdlan-injected SKG mouse model, highlighting mechanical stress as a critical aggravating factor in AS progression.